Reference: CD Antigens 2002 David Mason, Pascale André, Armand Bensussan, Chris Buckley, Curt Civin, Edward Clark, Masja de Haas, Sanna Goyert, Martin Hadam, Derek Hart, Václav Horejsí, Stefan This information is current as Meuer, James Morrissey, Reinhard Schwartz-Albiez, Stephen of September 25, 2021. Shaw, David Simmons, Mariagrazia Uguccioni, Ellen van der Schoot, Eric Vivier and Heddy Zola J Immunol 2002; 168:2083-2086; ; doi: 10.4049/jimmunol.168.5.2083

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References This article cites 1 articles, 0 of which you can access for free at: http://www.jimmunol.org/content/168/5/2083.full#ref-list-1 http://www.jimmunol.org/

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The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. ● REFERENCE

CD Antigens 20021

David Mason,2 Pascale Andre´, Armand Bensussan, Chris Buckley, Curt Civin, Edward Clark, Masja de Haas, Sanna Goyert, Martin Hadam, Derek Hart, Va´clav Horˇejsˇı´, Stefan Meuer, James Morrissey, Reinhard Schwartz-Albiez, Stephen Shaw, David Simmons, Mariagrazia Uguccioni, Ellen van der Schoot, Eric Vivier, and Heddy Zola

The Proceedings of the 7th Human Leukocyte Differen- Selection of antibodies Downloaded from tiation Antigen (HLDA) Workshop are about to be pub- With these considerations in mind the 7th Workshop adopted a T lished, detailing more than 80 new CD specificities. The different approach; instead of screening poorly characterized anti- next Workshop, planned for 2004, will continue this process, and bodies, reagents were selected (and actively solicited) for which at a number of candidate CD molecules in the literature, identified by least some molecular data were already available. A substantial antibody production or cloning, are listed in this update. number of monoclonal antibodies reactive with leucocyte-associ- ated molecules exist that do not meet the traditional criterion for http://www.jimmunol.org/ The tradition of HLDA Workshops establishing a new CD specificity (i.e., the existence of at least two The process of categorizing the antigenic molecules and epitopes independent antibodies of the same specificity). This rule dates associated with human white cells, via the collaborative study of from the first HLDA Workshop two decades ago; since that time, monoclonal antibodies, dates back to the early 1980s, when the biochemical and molecular biological techniques for characteriz- first HLDA Workshop was held in Paris, France. This initial meet- ing the targets of new antibodies have come to be widely used. ing listed only fifteen agreed molecular entities, but it created an In consequence, it is now considered appropriate to establish a internationally agreed basis for the nomenclature of leukocyte CD designation for a molecule if its gene has been cloned and molecules (the CD scheme), and also provided a forum for report- at least one specific monoclonal antibody has been studied in by guest on September 25, 2021 ing studies on their function and practical relevance. A further six the Workshop. HLDA meetings have been held since the first Paris meeting. The most recent of these (“HLDA7”) took place in 2000 in Harrogate, New Workshop sections U.K., and the proceedings of the meeting will be published this Four new sections were introduced in the 7th HLDA Workshop to year (Leucocyte Typing VII, Oxford University Press). add to the traditional list from past meetings: namely Dendritic The aims and approaches of the 7th HLDA Cells, Stem/Progenitor Cells, Erythroid Cells, and Carbohydrate Structures. Although it has been recognized for many years that Workshop monoclonal antibodies reactive with human leukocytes can be spe- The limitations of “blind” antibody screening cific for carbohydrate epitopes (e.g., the carbohydrate CD category It was apparent at the previous meeting, HLDA6, held in Kobe, CD15 was identified at the first Workshop), they had not received Japan, in 1996, that the technique of detecting molecular entities specific attention in any Workshop. The inclusion of erythroid by screening coded panels of monoclonal antibodies against hu- molecules, although it may seem out of place in a “Leukocyte man cells was becoming obsolete. Antibodies to the most immu- Workshop,” was justified by the number of molecules shared be- nogenic molecules had already been produced, and fewer labora- tween white and red cells (e.g., cytokine receptors) that hint at tories than in the early days were prepared to devote resources to unexplored functions of red cells. raising new antibodies, since the probability of finding novel re- agents becomes ever less likely. In consequence, many antibodies The yield of new CD specificities in the 7th in the 6th Workshop were reagents (submitted by laboratories that HLDA Workshop were not equipped to characterize them) which proved to be of This more active approach to the identification of new CD speci- known specificity. ficities represented a break with tradition, but the results justified the new approach, since a total of well over 80 new entities were Received for publication June 27, 2001. Accepted for publication January 10, 2002. added to the list of CD specificities. This compares favorably with The costs of publication of this article were defrayed in part by the payment of page previous Workshops (an average of less than 30 CD specificities charges. This article must therefore be hereby marked advertisement in accordance per Workshop), and it also largely avoided the laborious screening with 18 U.S.C. Section 1734 solely to indicate this fact. in multiple laboratories of antibodies that prove to be directed 1 By permission of Oxford University Press. against known CD molecules. 2 Address correspondence and reprint requests to Prof. David Y. Mason, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Tables I and II list the new specificities established at the 7th Hospital, Oxford OX3 9DU, U.K. E-mail address: [email protected] Workshop. Full details will be found in Leucocyte Typing VII, and

Copyright © 2002 by The American Association of Immunologists 0022-1767/02/$02.00 ● 2084 CD ANTIGENS 2002

Table I. New CD designations

CD Designation Name Section Locus Link

CD15u Sulphated CD15 Carbohydrate structures CD60a GD3 Carbohydrate structures CD60b 9-O-acetyl-GD3 Carbohydrate structures CD60c 7-O-acetyl-GD3 Carbohydrate structures CD75 Lactosamines Carbohydrate structures CD75s ␣-2,6-sialylated lactosamines (formerly Carbohydrate structures CDw75 and CDw76) CD85 ILT/LIR family (see Table II) Dendritic cells CD110 MPL, TPO R Platelets 4352 CD111 PRR1/Nectin1 Myeloid cells 5818 CD112 PRR2 Myeloid cells 5819 CD133 AC133 Stem/progenitor cells 8842 CD156b TACE/ADAM17 Adhesion structures 6868 CD158 KIR family (see Table II) NK cells CD159a NKG2A NK cells 3821 CD160 BY55 T cells 11126 CD162R PEN5 NK cells 6404 CD167a Discoidin domain R (DDR1) Adhesion structures 780 CD168 RHAMM Adhesion structures 3161 CD169 Adhesion structures 6614

CD170 Siglec-5 Adhesion structures 8778 Downloaded from CD171 Adhesion structures 3897 CD172a SIRP ␣ Adhesion structures 8194 CD173 Blood group H type 2 Carbohydrate structures CD174 Lewis y Carbohydrate structures CD175 Tn Carbohydrate structures CD175s Sialyl-Tn Carbohydrate structures CD176 TF Carbohydrate structures CD177 NB1 Myeloid cells

CD178 Cytokine/chemokine receptors 356 http://www.jimmunol.org/ CD179a Vpre-B B cells 7441 CD179b ␭5 B cells 3543 CD180 RP105 B cells 4064 CD183 CXCR3 Cytokine/chemokine receptors 2833 CD184 CXCR4 Cytokine/chemokine receptors 7852 CD195 CCR5 Cytokine/chemokine receptors 1234 CDw197 CCR7 Cytokine/chemokine receptors 1236 CD200 OX2 Nonlineage molecules 4345 CD201 EPC R Endothelial cells 10544 CD202b Tie2 (Tek) Endothelial cells 7010 CD203c NPP3/PDNP3 Myeloid cells 5169

CD204 Macrophage scavenger R Myeloid cells 4481 by guest on September 25, 2021 CD205 DEC205 Dendritic cells 4065 CD206 Macrophage mannose R Dendritic cells 4360 CD207 Dendritic cells 50489 CD208 DC-LAMP Dendritic cells CD209 DC-SIGN Dendritic cells 30385 CDw210 IL-10R Cytokine/chemokine receptors 3587;3588 CD212 IL-12R Cytokine/chemokine receptors 3594 CD213a1 IL-13R␣1 Cytokine/chemokine receptors 3597 CD213a2 IL-13R␣2 Cytokine/chemokine receptors 3598 CDw217 IL-17R Cytokine/chemokine receptors 23765 CD220 Insulin R Nonlineage molecules 3643 CD221 IGF1 R Nonlineage molecules 3480 CD222 Mannose-6-phosphate/IGF2 R Nonlineage molecules 3482 CD223 LAG-3 Nonlineage molecules 3902 CD224 ␥-glutamyl transferase Nonlineage molecules 2678 CD225 Leu13 Nonlineage molecules 8519 CD226 DNAM-1 (PTA1) T cells 10666 CD227 MUC.1 Nonlineage molecules 4582 CD228 Nonlineage molecules 4241 CD229 Ly9 Nonlineage molecules 4063 CD230 Prion Nonlineage molecules 5621 CD231 TALLA-1/A15 Nonlineage molecules 7102 CD232 VESP R Nonlineage molecules 10154 CD233 Band 3 Erythroid cells 6521 CD234 Fy-glycoprotein (DARC) Erythroid cells 2532 CD235a Erythroid cells 2993 CD235b Glycophorin B Erythroid cells 2994 CD235ab Glycophorin A/B crossreactive mAbs Erythroid cells CD236 /D Erythroid cells CD236R Glycophorin C Erythroid cells 2995 CD238 Kell Erythroid cells 3792 CD239 B-CAM Erythroid cells 4059 CD240CE Rh30CE Erythroid cells 6006 CD240D Rh30D Erythroid cells 6007 CD240DCE Rh30D/CE crossreactive mAbs Erythroid cells CD241 RhAg Erythroid cells 6005 CD242 ICAM-4 Erythroid cells 3386 CD243 MDR-1 Stem/progenitor cells CD244 2B4 NK cells 51744 CD245 p220/240 T cells CD246 Anaplastic lymphoma kinase T cells 238 CD247 ␨-chain T cells 919 The Journal of Immunology 2085

Table II. New CD nomenclature for ILT/LIR and KIR moleculesa molecular, functional, and other data can be found for many of these new specificities on the Protein Reviews on the Web CD Designation Name (PROW) Web site (http://www.ncbi.nlm.nih.gov/prow/).

The ILT/LIR family CD85a ILT5/LIR3 The 8th Workshop CD85b ILT8 Plans are well advanced for the 8th Workshop (see www. CD85c LIR8 CD85d ILT4/LIR2, MIR10 hlda8.org), to be organized in Adelaide, Australia, in 2004 under CD85e ILT6/LIR4 the aegis of Prof. H. Zola (Child Health Research Institute, CD85f ILT11 Adelaide, Australia). It is sometimes assumed that the catalog of CD85g ILT7 CD85h ILT1/LIR7 surface molecules associated with human hemopoietic cells is now CD85i LIR6 essentially complete, but there is abundant evidence in the litera- CD85j ILT2/LIR1, MIR7 ture for novel surface molecules that would merit study at the next CD85k ILT3/LIR5 CD85l ILT9 Workshop, and that could provide the basis for new CD designa- CD85m ILT10 tions. Table III comprises a list of potential new molecules re- The KIR family ported following the production of monoclonal antibodies, and CD158z KIR3DL7/KIRC1 CD158b1 and KIR2DL2/p58.2 and also a more extensive list of surface molecules identified via gene CD158b2 KIR2DL3/p58.3 cloning. In most instances, no antibodies are available against the CD158a KIR2DL1/p58.1 putative new leukocyte/endothelial markers in this latter group.

CD158c KIR2DS6/KIRX Downloaded from CD158d KIR2DL4 Specific and well characterized reagents, whether monoclonal or CD158e1 and KIR3DL1/p70 and polyclonal, are needed not only for detecting these new “virtual” CD158e2 KIR3DS1/p70 molecules but also for defining functional domains, for character- CD158f KIR2DL5 CD158g KIR2DS5 izing three-dimensional protein structure, and for analyzing pro- CD158h KIR2DS1/p50.1 tein-protein interactions. It may be added that cloning of gene CD158i KIR2DS4/p50.3 sequences often reveals multiple members of new or existing CD158j KIR2DS2/p50.2 CD158k KIR3DL2/p140 molecular families (e.g., the Toll-like receptors) and may identify http://www.jimmunol.org/ surface receptors that bind more than one ligand or vice versa, a For further details of this classification, based on the position of the on 19q;13.4 from centromeric to telomeric loci, see Ref. 1. (e.g., the TALL-1 and APRIL ligands for TACI and BCMA). Furthermore, a number of leukocyte-associated markers have been cloned from mice and other species, and almost all will have human homologues. The 8th Workshop will provide a forum for a

Table III. Examples of possible future CD specificities by guest on September 25, 2021 Molecule Molecule Size Cell Types Comments Refs.

Identified following antibody production AM-3K antigen 70 and 120 kDa Macrophages Zeng L. et al., J. Pathol. 1996; 178:207. BDCA-2, BDCA-3, and Dendritic cells Identifies subsets of dendritic cells Dzionek A. et al., J. Immunol. BDCA-4 antigens 2000; 165:6037. BENE 17 kDa Endothelium “Raft-associated” member of de Marco et al., J. Biol. Chem. MAL family; interacts with 2001; 276:23009. caveolin-1 CMRF-44 ? Dendritic cells Differentiated/activated Hock B. D. et al., Immunology 1994; 83:573. CMRF-56 95 kDa Dendritic cells Differentiated/activated Hock B. D. et al., Tissue Antigens 1999; 53:320. H47 antigen 100 kDa (non T cells and most NK, B cells ? Involved in T cell activation Hirohashi N. et al., Cell red.) 120 and monocytes Immunol. 1993; 152:371. kDa (red.) Hal-1 200 kDa (100 T cells, EBV-transformed ? New lymphoma marker Asanuma H. et al., Br. J. kDa) B-cells, myelomonocytic Haematol. 1999; 106:55. cells, anaplastic large cell lymphoma LAK1 and LAK2 120 kDa and LGL and LAK cells Zocchi M. R. et al., Cell antigens 110 ϩ 140 Immunol. 1989; 124:144. kDa respectively NKp80 80 kDa dimer NK cells and CD56-positive Novel member of the killer cell Vitale M. et al., Eur. T cells lectin-like gene family, J. Immunol. 2001; 31:233. encoded by KLRF1 gene; Roda-Navarro P. et al., Eur. triggers NK cell cytotoxicity J. Immunol. 2000; 30:568. VAP-1 (vascular 90 kDa Endothelium Mediates lymphocyte-endothelial Bono P. et al., J. Immunol. adhesion protein) adhesion; has monoamine 1998; 160:5563. oxidase activity Salmi M. and Jalkanen S. Science 1992; 257:1407. Wue-1 antigen 94 kDa Plasma cells Stimulates growth of plasma cells Greiner A. et al., Virchows Arch. 2000; 437:372. (Table continues) 2086 CD ANTIGENS 2002

Table III. Continued

Molecule Molecule Size Cell Types Comments Refs.

Identified via gene cloning B cell maturation factor 184 aa B cells TNFR family member; receptor Madry et al., Int. Immunol. (BCMA) for TALL-1 and APRIL 1998; 10:1693. Shu H. B. and Johnson H., Proc. Natl. Acad. Sci. USA 2000; 97:9156. B7-H2 302 aa Dendritic cells New member of B7 family; binds Wang S. et al., Blood 2000; ICOS on activated T cells 96:2808. CLEC-1 280 aa Dendritic cells Novel C-type lectin-like receptor Colonna M. et al., Eur. with cytoplasmic tyrosine-based J. Immunol. 2000; 30:697. motif CMRF-35A 224 aa NK cells, neutrophils, Novel Ig superfamily receptors. Jackson et al., Eur. J. monocytes, dendritic cells CMRF-35H contains 3 Immunol. 1992; 22:1157. and subset of T cytoplasmic tyrosine based lymphocytes motifs CMRF-35H 300 aa Green et al., Int. Immunol. 1998; 10:891. CS1 NK cells Novel receptor belonging to CD2 Boles K. S. et al., subset of Ig superfamily Immunogenetics 2001; 52: Downloaded from 302. DC-STAMP 470 aa Dendritic cells Novel protein containing seven Hartgers F. C. et al., Eur. putative transmembrane J. Immunol. 2000; 30:3585. domains. EMR3 652 aa Mainly leukocyte restricted; Novel EGF-TM7 molecule. Stacey M. et al., J. Biol. highest levels on Interacts with a surface ligand Chem. 2001; 276:18863.

neutrophils, monocytes on myeloid cells. http://www.jimmunol.org/ and macrophages Flt-1 (VEGFR-1) Endothelial cells, monocytes Sawano A. et al., Blood 2001; 97:785. GPRv53 390 aa Leukocytes Identified by gene cloning; G- Oda T. et al., J. Biol. Chem. protein-coupled histamine 2000; 275:36781. receptor IRTA1 and IRTA2 Subpopulations of B cells Homologous to the Fc and Hatzivassiliou G. et al., inhibitory receptor families Immunity 2001; 14:277. M160 1453 aa Macrophages New member of scavenger Gronlund J. et al., J. Immunol. receptor cysteine-rich 2000; 165:6406. superfamily by guest on September 25, 2021 MARCO (macrophage 520 aa Macrophages Class A scavenger receptor; Elomaa et al., J. Biol. Chem. receptor with collagenous involved in bacterial clearance 1998; 273:4530. structure) in vivo Van der Laan L. J. et al., J. Immunol. 1999; 162:939. TACI 293 aa B cells TNFR family member. Receptor Xia X. Z. et al., J. Exp. Med. for TALL-1 and APRIL 2000; 192:137. TREM-1 and TREM-2 Neutrophils and subset of Novel Ig superfamily receptors. Bouchon A. et al., J. Immunol. (triggering receptors monocytes (TREM-1) and TREM-1 triggers neutrophil 2000; 164:4991. expressed on myeloid macrophages (TREM-2) secretion (e.g. IL-8) and Daws M. R. et al., Eur. cells) degranulation; TREM-2 J. Immunol. 2001; 31:783. activates macrophages; both associate with DAP12. range of antibody-based studies relating to this accumulating leukocyte molecules that are localized within the cell cytoplasm corpus of genomic and proteomic data. (or nucleus). Given the importance of many of these molecules in As in the 7th Workshop in which four new sections were added, signaling pathways initiated via known surface CD molecules, it may be possible to include neuronal cells in the 8th Workshop. their identification and study is an inevitable extension of the work Many neuronal cells express cell surface found on leuko- of the first seven HLDA Workshops. Whether or not a new “in- cytes and vice versa (e.g., CD56, CD100, CD168, and CD171). tracellular CD” categorization scheme is devised for such mole- Furthermore, the guidance cues used by neuronal cells share cules, they are of interest for many laboratories interested in hu- similarities to those involved in leukocyte extravasation so the ex- man hematopoietic cells, and their study will be among the aims of pression of these molecules in common may reflect shared biolog- the next Workshop. ical processes. It may also be noted that other molecules such as the mucins thought to be primarily associated with epithelial cells, are now being described on leukocytes. Reference 1. Andre´, P., R. Biassoni, M. Colonna, D. Cosman, L. L. Lanier, E. O. Long, M. Finally, it remains to be established how the 8th and subsequent Lopez-Botet, A. Moretta, L. Moretta, P. Parham, et al. 2001. New nomenclature HLDA Workshops should deal with lineage- or stage-restricted for MHC receptors. Nat. Immunol. 2:661.